Extracellular matrix stiffness controls Transposable Elements through Pin1 to promote immune evasion in breast cancer.

ECM rigidity in breast cancer stabilizes Pin1, driving its nuclear accumulation to suppress LINE1 and other transposable element activity by preserving heterochromatin and nuclear envelope integrity.

• Why it matters: Stiff ECM–linked immune evasion in breast cancer is incompletely understood, especially how mechanical cues translate into genome regulation that affects immune recognition.
• What they did: The study links ECM stiffness to Pin1 phosphorylation-dependent stabilization and nuclear localization, then tests Pin1 loss or inhibition for heterochromatin relaxation, LINE1 reactivation, and cGAS/STING/type I interferon activation.
• The result: Pin1 depletion induces TE-derived neoantigen generation and remodels the tumor immune microenvironment, enhancing innate and adaptive immune responses and sensitizing fibrotic, immune-cold tumors to immune checkpoint blockade.